Homer2 and Homer3 interact with amyloid precursor protein and inhibit Abeta production

The study of Amyloid Precursor Protein (APP) processing has been the focus of considerable interest, since it leads to Aβ peptide generation, the main constituent of neuritic plaques found in brains of Alzheimer's disease patients. Therefore, the identification of novel APP binding partners that regulate Aβ peptide production represents a pharmaceutical target aiming at reducing Αβ pathology. In this study, we provide evidence that Homer2 and Homer3 but not Homer1 proteins interact specifically with APP. Their expression inhibits APP processing and reduces secretion of Aβ peptides. In addition, they decrease the levels of cell surface APP and inhibit maturation of APP and β-secretase (BACE1). The effects of Homer2 and Homer3 on APP trafficking to the cell surface and/or on APP and BACE1 maturation could be part of the mechanism by which the expression of these proteins leads to the significant reduction of Aβ peptide production.     

Minimally invasive parathyroidectomy in patients with previous endocrine surgery

Objective:

Previous endocrine neck surgery (PENS) in patients with sporadic primary hyperparathyroidism (PHP) is considered a contraindication for minimally invasive parathyroidectomy (MIP). The purpose of our study was to determine the effectiveness of MIP in such patients.

Methods:

From January 2004 to December 2009, 270 patients with PHP were treated in our department; 30 had had PENS in the past. Eighteen were selected to have MIP, while the other 12 had traditional neck explorations. Selection criteria for MIP were unilateral single- or double-gland disease localized preoperatively with at least 2 concordant imaging techniques and patient informed consent. Imaging studies included high-resolution neck ultrasound and sestamibi scan in most patients, and CT scan, selective venous sampling, and MRI in 7 patients. Unilateral explorations via a lateral approach with the patients under local (UALA in 13 patients), general (MIP in 4 patients), or local followed by general anesthesia (1 patient) were performed.

Results:

Sixteen of the 17 patients became normocalcemic after the operation. There was no conversion to traditional exploration. A single adenoma was found in 16 patients and hyperplasia in one. One patient underwent a successful parathyroidectomy 8 months later via mesothoracoscopy, because the parathyroid gland was localized correctly but was beyond access via neck. There were no postoperative complications. Mean duration of the procedure and length of stay were similar to MIP in patients without PENS. Mean follow-up of 33 months (range, 4 to 70) did not reveal any recurrence.

Conclusion:

These results illustrate that MIP is a valuable option in select patients with sporadic PHP and PENS. Localization with 2 or more concordant imaging techniques could avoid intraoperative sestamibi or qPTH testing with low morbidity (0%), high biochemical cure rate (100% in this series), rapid recovery, and finally substantially lower the cost of the procedure.     

An efficient method for studying short-term plasticity with random impulse train stimuli

In this article, we introduce an efficient method that models quantitatively nonlinear dynamics associated with short-term plasticity (STP) in biological neural systems. It is based on the Voterra-Wiener modeling approach adapted for special stimulus/response datasets. The stimuli are random impulse trains (RITs) of fixed amplitude and Poisson distributed, variable interimpulse intervals. The class of stimuli, we use can be viewed as a hybrid between the paired impulse approach (variable interimpulse interval between two input impulses) and the fixed frequency approach (impulses repeated at fixed intervals, varying in frequency from one stimulus dataset to the next). The responses are sequences of population spike amplitudes of variable size and are assumed to be contemporaneous with the corresponding impulses in the RITs they are evoked by. The nonlinear dynamics of the mechanisms underlying STP are captured by kernels used to create compact STP models with predictive capabilities. Compared to similar methods in the literature, the method presented in this article provides a comprehensive model of STP with considerable improvement in prediction accuracy and requires shorter experimental data collection time.     

Nicotinic receptor modulation: advantages for successful Alzheimer's disease therapy

Galantamine is a modest acetylcholinesterase inhibitor (AChEI) that is also an allosteric potentiating ligand (APL) of nicotinic acetylcholine receptors (nAChRs). In this report, these two effects are shown to be dependent upon each other using a realistic computer model of the cholinergic synaptic cleft. The model is based upon realistic estimates of the anatomy of a neuronal synapse, the kinetic states of pre- and postsynaptic nAChRs, and the acetylcholinesterase enzyme. The number of open postsynaptic nAChRs per action potential is a measure of cholinergic neurotransmission. Using mathematical equations and published data, the effect of the AChEI and APL actions of galantamine is quantitatively described and compared to the effects of pure AChEIs. The model shows that galantamine--compared to similar concentrations of pure AChEIs--is able to compensate for its somewhat modest effect on the cholinesterase enzyme with its allosteric modulatory effects that include the additional benefit of a lower degree of receptor desensitization.     

An introductory course for training in endoscopy

Endoscopy practice must respect the ethical aspects of medicine, and the principles of humanism must be reinforced when teaching endoscopy. A well-organized, structured training is essential if we are to ensure that procedures are performed in a safe and effective manner. The most difficult period of training is with the novice endoscopist, so we recommend the introduction of a structured pre-endoscopy training curriculum. This should ideally include introductory lectures and courses, the use of didactic videotapes and training in endoscopy on a computer-based simulator. We also advocate 'train the trainers' international courses to encourage a uniform approach to the teaching of endoscopy. Their aim will be to educate skilled endoscopists in the principles of teaching, which should be thoroughly grounded in the ethics of our profession.     

Superinfection of chronic multifocal osteomyelitis with Enterobacter cloacae

A case is presented of a 6-year-old boy from Nigeria who developed chronic multifocal osteomyelitis with bilateral and symmetrical proximal humeral involvement. Superimposed changes of acute osteomyelitis were noted on the histopathological evaluation of the lesions. Cultures from both sides were positive for Enterobacter cloacae, which was presumably contracted during intravenous therapy for typhoid fever in Nigeria 1 month prior to his presentation.     

Diagnosis and management of lateral sinus thrombosis.

OBJECTIVES: To define the contemporary management of septic otogenic lateral sinus thrombosis. STUDY DESIGN: Retrospective case series identified through database search of otologic surgical cases managed by a single surgeon in four teaching hospitals over a 6-year period. METHODS: Twelve patients presenting with lateral sinus thrombosis of otogenic cause were the subjects of this study. Patients with incomplete medical records or unknown outcomes were excluded. RESULTS: Lateral sinus thrombosis was the result of chronic otitis media in 50% of cases, with five of these patients having cholesteatoma. In addition, there were seven associated intracranial complications in six patients in this series. All patients underwent medical and surgical treatment. Aggressive and early surgical treatment was tailored to the degree of preoperative and intraoperative findings. The sigmoid sinus was resected in six of the patients with a variable degree of inferior margin proportional to the extent of thrombosis. Thrombectomy alone under vascular control with reestablishment of flow was used to remove the septic thrombus in the other six patients. There were no complications in these patients. CONCLUSION: Early and aggressive surgical intervention of this otogenic complication can potentially minimize mortality, hospital stay, and length of medical treatment.